Influence of Inflammation on Assessing Iron-Deficiency Anemia in Cuban Preschool Children

Abstract

INTRODUCTION Anemia is a public health problem worldwide and is most prevalent in preschool children, for whom it is the most frequent cause of nutritional defi cits. In turn, iron defi ciency is the main cause of anemia, affecting 43% of children globally. Previous studies in Cuba show rates of iron defi ciency in preschool children between 38.6% and 57.6%, higher in infants (71.2% to 81.1%). WHO recommends using serum ferritin as an indicator of iron defi ciency accompanied by acute (C-reactive protein) and chronic (α1-acid glycoprotein) infl ammation biomarkers. OBJECTIVE Assess how infl ammation affects measuring and reporting of iron-defi ciency anemia rates in Cuban preschool children.METHODS Data were obtained from serum samples contained in the National Anemia and Iron Defi ciency Survey, and included presumably healthy preschool Cuban children (aged 6-59 months). Serum samples were collected from 1375 children from randomly selected provinces in 4 regions of the country from 2014 through 2018. We examined the association between ferritin and two infl ammatory biomarkers: C-reactive protein and α1-acid glycoprotein. Individual infl ammation-adjusted ferritin concentrations were calculated using four approaches: 1) a higher ferritin cut-off point (<30 g/L); 2) exclusion of subjects showing infl ammation (C-reactive protein >5 mg/L or α1-acid glycoprotein >1 g/L); 3) mathematical correction factor based on C-reactive protein or α1-acid glycoprotein; and 4) correction by regression with the method proposed by the Biomarkers Refl ecting Infl ammation and Nutritional Determinants of Anemia Group. We estimated confi dence intervals of differences between unadjusted prevalence and prevalence adjusted for infl ammation by each method. RESULTSThe proportion of children with infl ammation according to C-reactive protein concentrations >5 mg/L was lower (11.1%, 153/1375) than the proportion measured according to the concentrations of α1-acid glycoprotein, at >1 g/L (30.8%, 424/1375). The percentage of children with high concentrations of at least one of the aforementioned biomarkers was 32.7% (450/1375). Thus, each correction method increased the observed prevalence of iron defi ciency compared to unadjusted estimates (23%, 316/1375). This increase was more pronounced when using the internal regression correction method (based only on C-reactive protein) or the method based on a higher cut-off point. Adjustment using all four methods changed estimated iron defi ciency prevalence, increasing it from 0.1% to 8.8%, compared to unadjusted values. CONCLUSION One-third of preschool children had biomarkers indicating elevated infl ammation levels. Without adjusting for infl ammation, iron defi ciency prevalence was underestimated. The signifi cant disparity between unadjusted and infl ammationadjusted ferritin when using some approaches highlights the importance of selecting the right approach for accurate, corrected measurement. The internal regression correction approach is appropriate for epidemiological studies because...

Adjusting Iron Deficiency for Inflammation in Cuban Children Aged Under Five Years: New Approaches Using Quadratic and Quantile Regression

“…Coeffi cients estimated by linear regression for the sample of 1365 children were slightly diff erent than those obtained by Pita, [16] due to the exclusion of the 10 individuals with outliers in AGP and CRP values.…”

“…The BRINDA group [7] recommends using the upper limit of the fi rst decile of each biomarker as a reference value. Based on this criteria, Pita [16] obtained a CRP reference value of 0.10 mg/L and an AGP reference value of 0.54 g/L.…”

“…A detailed description of sample selection can be found in the aforementioned article by Pita. [16] Case defi nition Iron defi ciency was defi ned as ferritin concentration <12 μg/L, the cut-off point recommended by WHO. [2] Acute infl ammation was defi ned as CRP ≥5 mg/L and chronic infl ammation as AGP >1 g/L.…”

“…The most recent study on iron defi ciency in children aged under fi ve years supports the hypothesis that ferritin concentrations change in magnitude according to the state of infl ammatory processes in the fi rst fi ve years of life. [16] Iron status in Cuban children aged under fi ve years is modifi ed in the presence of infl ammation. [16] In Pita's study, [16] the ferritin concentrations of 1375 children were adjusted for infl ammation (measured by CRP and AGP), using four of the most well-known approaches in recent literature: a) higher ferritin cut-off point (>30 g/L); b) excluding subjects with infl ammation (CRP >5 mg/L or AGP >1 g/L); c) CRP-or AGP-based arithmetic correction factors; and d) regression correction using the method proposed by the BRINDA group (Biomarkers Refl ecting Infl ammation IMPORTANCE This study demonstrates the usefulness of two new approaches for correcting ferritin concentrations in the presence of infl ammation, which would improve methods for evaluating iron defi ciency in Cuban children aged under fi ve years , and thus provide more reliable data on iron defi ciency prevalence in the country.…”

The Influence of Intensive Nutritional Education on the Iron Status in Infants

“…Various factors can influence the iron status in children, such as socioeconomic status, demography, the type of milk consumed by infants, dietary intake, elevated inflammation levels (e.g., C-reactive protein) and gastrointestinal diseases [15,18,[34][35][36][37][38]. Different studies confirmed that children from families from lower socioeconomic backgrounds, schooling and employment status; rural areas; and consuming less meat, fruits, and more cow milk are more prone to iron deficiency [34][35][36][37][38]. Thus, outside of our parental nutritional education, many factors can influence iron status during infancy.…”